The Aneurysm Information Project

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    March 1998 - Papers of the Month
    
    1. Adolph R, et al.  Cellular content and permeability of
    intraluminal thrombus in AAA.  J Vasc Surg 1997;25:916-
    26.
    
    Purpose - "...the precise role of the intraluminal
    thrombus in the formation, enlargement, and rupture of
    AAA is unknown."
    
    Methods - "Tests performed were light, transmission, and
    scanning electron microscopy; fluid permeability
    measurements; and Western blots."
    
    Results - The thrombus "is structurally complex and is
    traversed...by a continuous network of interconnected
    canaliculi." There is "cellular penetration for at least
    1 cm from the luminal surface of the thrombus."  "Fibrin
    degradation occurred principally at the abluminal
    surface."
    
    
    Comment by mdt:  David Vorp at the Univ Pittsburgh and
    his colleagues are the first group to show much interest
    in recent years in this interesting feature of the AAA,
    namely its rather constant feature of intraluminal
    thrombus.  Ever since Eugene Bernstein and colleagues
    reported that the extent of thrombus had a correlation
    with the rate of enlargement, it has seemed clear that
    the role of the thrombus deserved closer attention. 
    Jessie Jean-Claude, first author of a paper from our
    laboratory, reported that plasmin is elevated in soluble
    extracts of AAA tissue.  Vorp and colleagues report that
    fibrin degradation is most intense in the thrombus
    adjacent to the aortic wall.  Since plasmin is an
    activator of the MMP's (which we and others have shown to
    be important mediators of aortic matrix destruction), it
    is possible that clot correlates with rate of aneurysm
    enlargement due to permeation of the aortic wall with
    plasmin from the thrombus.
    
    
    2. Boyle JR, et al.  Doxycycline inhibits elastin
    degradation and reduces metalloproteinase activity in a
    model of aneurysm disease.  J Vasc Surg  1998; 27: 354-
    61.
    
    Purpose - "The ability of doxycycline - an MMP inhibitor
    - to reduce matrix degradation was assessed in a ...
    model of aneurysmal disease that used a brief pulse of
    elastase to induce MMP production and elastin degradation
    in arterial organ culture."
    
    Methods - "Porcine aortic segments were incubated in
    exogenous pancreatic elastase for 24 hours before culture
    ... for 13 days with both 1 and 10 mg/L doxycycline."
    
    Results - "... a significant preservation of elastin in
    aorta treated with doxycycline 10 mg/L (p<0.001)." 
    "...this preservation was accompanied by a significant
    reduction in MMP-9 activity."  
    
    
    Comment by mdt:  This interesting paper is nicely
    illustrated and presented.  The results confirm a
    previous study from the Washington Univ (St. Louis)
    group, which used the Anidjar/Dobrin elastase infusion
    model in the rat.  Because of increased awareness of the
    importance of screening for AAA disease in our aging
    population, especially among those who have a family
    history, pharmacological approaches to the stabilization
    of small AAA's are becoming increasingly interesting.